Research in bioinorganic chemistry is continuing to reveal how proteins regulate the reactivity of metal ions for ligand binding and catalysis, and reciprocally, how metal ions influence the structure of dynamics of proteins. This research will extend previous work on the involvement of inorganic elements such as iron, cobalt, copper and zinc in biological processes with particular emphasis on copper. The recent discovery of organo-copper complexes in cancerous tissues has intensified studies of the interaction of nucleotides with copper, specifically the mutagenic, carcinogenic or cytotoxic effects that the electrophilic agents (H+, R+ and metal cations) have on the cell. Although studies have been conducted on the interaction between these electrophilic agents and monomeric constituents of nucleic acids, little work has been done regarding the site of attachment of the copper metal to these nucleotides. This study will investigate the interaction of nucleic bases (cytosine, adenine, guanine and thymine), their respective nucleoside and nucleotide forms, DNA and RNA with copper nanoparticles using surface enhanced Raman scattering (SERS) spectroscopy. The specific aims of this project are to determine the selectivity of the adsorption sites on the copper surfaces, as well as provide information regarding the site(s) of attachment, molecular forms and orientation of the nucleo-bases on the metal surfaces based on the SERS spectra. This work will incorporate isotopic editing of the nucleic bases in order to determine the vibrational modes associated with the active binding site for the various forms of the nucleotides, as well as the use of other metal substrates to determine metal specificity. These studies will be extended to include the effects of pH, counter ions and concentration. The long term goal of this project is to use the information contained in the SERS data to explain the nature of the nucleic-copper interactions in biological systems.